In macronuclei of hypotrichous ciliates all of the DNA is in gene-sized pieces. These come about during formation of a macronucleus after sexual conjugation. In this process micronuclear chromosomes first become polytene and are then cut by an endogenous nuclease into short segments. Most of the DNA in each segment is destroyed, leaving a gene-sized piece of DNA. This involves elimination of 95% of the nucleotide sequences in the original micronuclear chromosomes. Thus, the cell operates with only 5% of the nucleotide sequences in the genome (the macronucleus synthesizes all cellular RNA). E. coli plasmid (pBR322) has been used to clone all the macronuclear DNA molecules. Genes with identifiable functions are being sought among these plasmid hybrids. Macronuclear DNA has been fractioned by electrophoresis and genes for rRNA, tRNAs, and histones identified in particular DNA size classes. The DNA sequences in plasmids will be used to determine nucleotide sequences in macronuclear DNA, particularly in DNA of known genetic function.